Stem cells can have a strong sense of identity. Taken out of their home in the hair follicle, for example, and grown in culture, these cells remain true to themselves. After waiting in limbo, these cultured cells become capable of regenerating follicles and other skin structures once transplanted back into skin. It's not clear just how these stem cells - and others elsewhere in the body - retain their ability to produce new tissue and heal wounds, even under extraordinary conditions.
New research at Rockefeller University has identified a protein, Sox9, that takes the lead in controlling stem cell plasticity. In a paper recently published in Nature, the team describes Sox9 as a "pioneer factor" that breaks ground for the activation of genes associated with stem cell identity in the hair follicle.
"We found that in the hair follicle, Sox9 lays the foundation for stem cell plasticity," says study author Elaine Fuchs, PhD, Rebecca C. Lancefield Professor, Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development. "First, Sox9 makes the genes needed by stem cells accessible, so they can become active. Then, Sox9 recruits other proteins that work together to give these 'stemness' genes a boost, amplifying their expression. Without Sox9, this process never happens, and hair follicle stem cells cannot survive."
Sox9 is a type of protein called a transcription factor, which can act like a volume dial for genes. When a transcription factor binds to a segment of DNA known as an enhancer, it cranks up the activity of the associated gene. Recently, scientists identified a less common, but more powerful version: the super-enhancer. Super-enhancers are much longer pieces of DNA, and host large numbers of cell type-specific transcription factors that bind cooperatively. Super-enhancers also contain histones, DNA-packaging proteins, that harbor specific chemical groups - epigenetic marks - that make genes they are associated with accessible so they can be expressed.
"Importantly, we link this pioneer factor to super-enhancer dynamics, giving these domains a ‘one-two punch' in governing cell identity. In the case of stem cell plasticity, Sox9 appears to be the lead factor that activates the super-enhancers that amplify genes associated with stemness," Fuchs says. "These discoveries offer new insights into the way in which stem cells choose their fates and maintain plasticity while in transitional states, such as in culture or when repairing wounds."
[Source: Rockefeller University]